We will attempt to establish the etiology and pathogenesis of multiple sclerosis using several interdependent approaches. This objective is divided into four areas: 1) the isolation of mammalian oligodendrocytes; 2) analysis of glial cell plasma membranes; 3) virus infection and demyelinating diseases; and 4) immunologic mechanisms of demyelinative CNS disease. We will use immunologic techniques in an effort to determine the target antigen(s) in oligodendrocyte membrane which interacts with serum from patients with MS. We will characterize other circulating immunologic factors, including antibodies to lipid haptens and alterations in circulating immunocompetent cells. We will carry out similar studies in cells derived from cerebrospinal fluid of patients with MS as one approach to studies of the compartmentalization of the immune response in patients with MS. We will study the biosynthetic processes occurring in isolated oligodendrocytes and in glial cells and the factors which influence those processes. We will attempt to repeat the successful induction of CNS disease in sub-human primates inoculated with material from patients with CNS disease and study viruses isolated from these primates. We will study the mechanisms of resistance and susceptibility to latent virus infections in the CNS. Mechanisms of humoral and cell-mediated immunological reactions in patients and in animal models will continue to be explored. Viruses isolated in the course of these experiments will be characterized by immunological and biochemical techniques.